I know I’ve written about this issue before – and I guarantee I will write about it again – but I assure you it is important enough to be discussed until even after it has been resolved. The Randomized Controlled Trial (RCT) has become something greater than life. It is the foundation of all Guidelines; it is the subject of Board test questions; it is the trump card in all roundmanship controversies. RCTs have taken on a power beyond all other aspects of medical knowledge. And I am sure this fact represents one of Medicine’s most perilous errors. Instilling RCTs with veto power across all lines of medical debate has relegated such things as clinical acumen, understanding of pathophysiology, and good old-fashioned common sense to second-rate skills. Endowing the RCT with omnipotence has all but eliminated the need for doctors and other health care practitioners to read extensively and understand the fundamental principals of medicine. Two recent examples plainly illuminate this problem.

In one case, a woman with a history of breast cancer as well as ASCVD finished her fifth year of Arimidex. Should she continue was the question, even though the medication might have been making it more difficult to effectively manage her lipids. No study had resolved this issue and so she decided to discontinue the medication. Troubled by her decision I contacted her oncologist and asked him what his gut suggested we do. He favored continuation of the medication. We listened to his well-honed instinct and simply fought a bit harder to control her cholesterol. Last week she was one of the first to have a test to predict the value of Arimidex continuation beyond year five. It turns out that she has a very high risk of breast cancer recurrence in the absence of drug. In other words, the oncologist’s gut was spot on. Perhaps the decision saved her life.

In another case, a friend recently told me that since our conversation regarding his atrial fibrillation four years ago – when I had suggested he stop drinking seltzer and also increase his magnesium intake – he completely stopped experiencing episodes of Afib. At the time he was having such frequent bouts of arrhythmias that radiofrequency ablation was strongly advised by all his physicians. Fortunately he tried an unproved treatment (which I, an electrophysiologist, had seen work in other patients) and it was entirely effective. By trying something safe yet unproved, he was spared a potentially life-threatening procedure.

Reflecting on how we all practice medicine, I cannot but acknowledge the fact that most of our decisions are based upon data distinct from what can be found in the RCT. The bottom line: let’s respect and honor that which makes doctors more than just a commodity – our knowledge, instinct, clinical acumen, common sense, and sometimes our depth of caring.

The AHA 2014 Scientific Sessions are over and I have already written twice about IMPROVE IT but I feel compelled to write again. Although the media has been oddly silent about the trial (why is that I wonder???), I predict its fallout will greatly impact the disciplines of Cardiovascular Disease Prevention, Clinical Lipidology, and even the essence of clinical practice. The reasons are manifold. First, the trial proved two critical theories: a lower LDL cholesterol level is better, and statins are not the only way to achieve a clinically relevant LDL reduction. Additional key considerations from IMPROVE IT include:

Lower LDL in properly chosen patients (and probably almost everyone) yields lower rates of stroke and heart attack, the two most formidable foes of modern man. For example, in the trial, an LDL of 53 was significantly better than an LDL of 70. Should we doctors then aim for 40, or perhaps even 25?

In our high-risk patients should we consistently and continuously add medications to statins in order to drive cholesterol levels lower and lower? For example, in a patient with a prior heart attack is it now fair to accept 70 for an LDL when we know that 53 would decrease our patient’s chance of having a recurrent and potentially life-threatening event?

What do we do with the hotly debated 2013 ACC/AHA Cholesterol Guidelines? They eliminated LDL goals and allowed for the use of Zetia only with individualized – and typically time-prohibitive – clinician/patient discourse, but they did NOT encourage driving LDL lower than 70. The Guidelines advocated for an LDL response to therapy of > 50%. So where does that leave our heart patients who start with LDLs of 180, for example. If they achieve the intended LDL reduction of 50% and thereby remain with an LDL of 90 mg/dL the guidelines surely say all is well – job well done. They state there is no indication to go further. Well now there is an indication. Now we can say with certainty that an LDL of 53 is a far better goal than 90. Having an LDL of 90 leaves significant and now manageable residual risk. So then how can a health care provider in good conscience advocate keeping such a patient at an LDL that clearly conveys greater risk?

The Guidelines also strongly advocate our utilization of maximum statin doses prior to adding an agent like Zetia. Knowing that higher dose statins produce more side effects while yielding a diminishing return on cholesterol lowering, wouldn’t it now be more prudent for doctors to prescribe low dose statins in combination with Zetia? This would limit side effects while yielding lower LDL levels than would the Guideline recommended approach. More food for thought.

How will insurance providers respond to Improve-It’s results? After the ACC/AHA Guidelines’ release, with lightening speed they downgraded access to add-on therapies such as Zetia. Of course that saved them money. So what now? Will they respond in kind, follow the science, and quickly allow patients access to these medications? We shall see but I have my doubts. Profits it seems oftentimes take precedence over science and health.

One more crack at the Guidelines for now: It is true that we do not know what represents the optimal LDL cholesterol level in human beings. Based upon our ever-expanding understanding of lipids including our body’s limited need for extraneous cholesterol however, it is safe to say that that level is probably quite low, perhaps even as low as 25 or 30 mg/dL. And, given the fact that many of us are goal-oriented, wouldn’t it now make sense to join our friends across the pond as well as our very learned friends here at home in the National Lipid Association and simply reinstate LDL goals?

As I sit at my desk tapping these keys I am clearly frustrated by the politics and economics woven inextricably into the fabric of medical practice. But I am also comforted and encouraged by the knowledge that many of us have already spent the last decade and beyond practicing the way we felt the science dictated. And by so doing, in the matter of LDL-lowering with Zetia, for every 120 patients we’ve treated in an Improve-It style, we’ve saved 3 from enduring a stroke or heart attack. This fact renders all our struggles worthwhile.

On a final note let us not forget that doctors have NO financial incentive to prescribe these medications. Our only “dog in the fight” is protecting our patients from harm. Insurance providers often do have a financial incentive to preclude doctors from prescribing some medicines (typically those that cost them more money). So whom do you, the patients, want to be in control of your medication regimen – the more highly educated and clearly non-conflicted physicians, or the less knowledgeable and often-conflicted insurance carriers? The answer to me seems pretty clear.

The IMPROVE-IT verdict is in and it will change the practice of cardiovascular disease prevention. For the first time, a non-statin medication has been shown to reduce cardiovascular events (including stroke and MI) when added to a statin. Achieving an LDL level of 53 vs 70 by the end of the trial’s first year translated into a significant ASCVD risk reduction. The risk reduction is so substantial that in this patient population the “number needed to teat” was only 50. That means that for every 50 patients treated with Zetia on top of a statin, a serious/life-threatening event was prevented. And, there were no safety issues associated with adding Zetia. Thus, a downside was not present. There are so many ramifications of this trial; I will highlight a few:

As believed by most lipid (cholesterol) specialists, lower LDL is definitely better.

Many insurance companies will have to revisit their denials of Zetia – it has now been shown to be highly effective and must be a part of doctors’ armamentaria.

Other emerging medications that dramatically lower cholesterol – the PCSK9 inhibitors and possibly the CETP inhibitors – will likely lower ASCVD events in the right patients.

In patients with severe genetically caused high cholesterol – specifically those with Familial Hypercholesterolemia – doctors will try even harder to use varied tools to lower LDL as much as possible. This includes using LDL apheresis, a procedure that has frequently been denied coverage by many insurance carriers, even after experts have testified about its efficacy.

We have learned that an understanding of biology and pathophysiology, in the context of clinical experience and careful observation, should not be dismissed solely because of the absence of a large randomized controlled trial (RCT). Though it took an RCT to prove this point, those of us who have been using Zetia religiously for many years have borne witness to its efficacy. We did not need this trial to tell us how important the medication is in the management of ASCVD, but it surely makes us feel better (and a bit vindicated as well). Most consequentially, it is heartwarming to consider the vast numbers of patients we’ve helped avoid experiencing heart attacks and strokes as a result of our well-considered and steadfast convictions.

Tomorrow morning a large crowd will gather here at the AHA meetings in frigid Chicago to learn the findings of the long-awaited IMPROVE-IT trial. The trial will demonstrate whether or not Ezetamibe (Zetia) added to a Simvastatin (Zocor) successfully decreased cardiovascular events in high-risk patients.

Many lipid specialists and cardiologists, myself included, have used Ezetamibe in combination with statins since the drug’s release. We believe wholeheartedly in the “lower LDL is better” hypothesis. Our clinical results, though anecdotal, have been uniformly exceptional. We fully anticipate that – barring confounding circumstances – the trial will be a winner.

Making this prospect even more impactful is the current NEJM publication by Dr. S. Kathiresan, (a brilliant Harvard Cardiologist/Geneticist) describing a novel genetic mutation that decreases LDL cholesterol, and concomitantly reduces ASCVD events. Where is this mutation you might ask: In the same receptor that is blocked by the drug Ezetamibe. Essentially individuals bearing such a mutation are born with the equivalent of continual Zetia use. This experiment of nature surely supports the speculation that Ezetimibe effectively lowers heart disease, even on top of statin therapy.

For now, we can only speculate about IMPROVE-IT’s findings. Tomorrow will bring some hard facts along with an assessment of how the findings will impact not only doctors’ use of Ezetamibe, but equally importantly, how health insurance companies will view the matter as well. Until tomorrow my admittedly unbiased fingers will be tightly crossed.

On October 13th the world’s “who’s who” in FH research and patient care convened in an oddly elongated New York City hotel meeting room. For two days the group shared novel information, spontaneous ideas, well-conceived proposals for future research, and even heart wrenching stories from a handful of brave and resilient FH patients. Windowless room notwithstanding, leaders from the Netherlands, South Africa, Australia, Chile, Russia, France, Sweden, Oman and the US uniformly basked in the bliss of a mutual goal, raising awareness and improving treatment for this far too common and oft-unrecognized disease.

Some of the highlights included a one-year review of the FH Foundation’s CASCADE FH Registry. We were all pleased and proud to learn that the Registry had surpassed its forecast goal by over 30% (Actually by over 400% of a more modest prediction). We travelled the world identifying FH “Gaps Across the Globe.” During this session leaders from diverse nations compared and contrasted barriers to care, offering useful methods to hurdle such obstacles. We heard from a continuum of clinicians – internists, lipid specialists, endocrinologists, cardiologists, and gastroenterologists – as well as PhDs occupying a wide range of disciplines. To say the conference was comprehensive fails to express its exceptionality. It was a time apart from other times, a transcendent growth opportunity for all those fortunate enough to be in attendance. It will surely serve as a solid springboard for meaningful clinical collaborations throughout the next year.

In sum, the 2014 FH Global Summit was so spectacular it will be hard to surpass in 2015. However, considering the passion and energy shared by members of the FH Foundation and colleagues across the globe, I feel safe in predicting that 2015 will exceed even the extraordinariness of this year’s event.

The Internet teems with self-proclaimed experts in every discipline. They exercise free speech saying whatever they choose, ignoring all consequences. The freedom to speak one’s mind is a right that can never be eroded; yet it must be wielded with responsibility and intellectual honesty. And herein lies a pervasive problem. People who know very little are saying an awful lot. In the case of cholesterol, erroneous information can lead to unnecessarily dire consequences – heart attacks, strokes, and even death. Let’s look at LDL, what we know to be true and what we also know to be false.

LDL is a lipoprotein particle that carries cholesterol in our blood. Cholesterol requires such a transporter, as it would crystalize without it. (Knife-like crystals would then literally tear apart the linings of our blood vessels. Not a pretty image!) LDL’s main purpose is to deliver its cargo, leftover cholesterol, to our liver for disposal. It does not – I repeat, it does NOT – carry cholesterol to any other part of our body to be used for beneficial purposes. But many on the Internet say otherwise. They use our body’s undeniable need for cholesterol as evidence that LDL is necessary for brain health, hormone production, and optimal cellular function. And yet there is absolutely no evidence to support their claim. They state that lowering LDL with medications like the statins can lead to dementia and general cellular dysfunction (among countless other things). Their contention is that lowering LDL will leave our cells starving for cholesterol. Again, there is no evidence to support this. And, what they neglect to tell their readers is that every cell in our body has the capacity to make its own cholesterol. So if levels become too low, cells turn up their cholesterol-manufacturing system and create as much as they need. These charlatan fear-mongers also fail to let their information-craving audience know two essential facts. First, LDL undeniably causes vascular disease. And second, statins have unequivocally been shown to reduce heart attacks, strokes, and death.

Supporting the first fact are century-old trials that validate the causal relationship between LDL and cardiovascular disease. But the most compelling information has come on the scene only just recently. Proof positive (to the best of our current scientific capacity) comes in the form of Mendelian Randomization studies (MR studies). These studies use the random assortment of genes during the process of reproduction to eliminate what we call “confounders”, conditions that falsely produce findings while oftentimes going unrecognized. MR studies are actually nature’s superior form of Randomized Controlled Trials (RCT), the bedrock of modern science. And, to date, every LDL MR study has consistently shown that LDL is more than simply associated with cardiovascular disease; it is a major cause. Patients with genetically low LDL are protected from disease, while those with genetically high LDL, such as Familial Hypercholesterolemia (FH) patients, are besieged by disease. In sum, high LDL is bad. Don’t let anyone tell you otherwise.

The second fact is also backed by innumerable studies and clinical trials. Statins – when given to the right patients – decrease heart attacks, strokes, and death. Statins save lives. Again, please don’t let anyone try to convince you otherwise. As to who are the “right” people to receive statins, we have guidelines to help us decide, but the ultimate decision is one that should be made between patient and physician.

The bottom line, whether it is with LDL or any other serious issue we strive to understand, we must all be very careful about our sources. My credo is to always find a primary resource. In the case of LDL, read and listen to the real experts, those who spend their lives understanding the issues with the sole goal of helping patients become healthier and live longer, better lives.

Two weeks ago was the ASPC’s Annual meeting in Boca Raton, FL. The event was superb. Internationally recognized experts in a variety of disciplines convened in Boca Raton for the three–day-event. Nearly 200 healthcare practitioners from around the country came to listen to Professors from Northwestern, Harvard, NYU, The Mayo, Columbia University, The Miami Miller School of Medicine, Emory, Ohio State, UCLA… Topics such as the somewhat controversial 2013 ACC/AHA Cholesterol and Obesity Guidelines, the enormously under-recognized disorder Familial Hypercholesterolemia, and the vast sex differences in CVD presentation and treatment were discussed.

My lecture was entitled, “The Omega-3 Fatty Acids DHA and EPA: Caution when interpreting the Trials. It’s time to get back to the basics.” The talk highlighted enormous limitations inherent in recent omega-3 studies. It is not only clinicians and laypeople who must understand such issues, but the press as well. Too many reporters – and even physicians in the news – misinterpret clinical studies, oftentimes sending not just misleading messages to the pubic, but potentially damaging ones as well.

DHA and EPA are the essential fatty acids found in fish, NOT flax, Chia, or olive/canola oil. These fatty acids have been studied in a variety of disorders ranging from heart attacks to dementias, ADHD, eye disease, inflammatory bowel disorders, and Rheumatologic ailments. The list is actually even more extensive than this. Their benefits are legion – anti-inflammatory, anti-oxidant, anti-arrhythmic, and anti-thrombotic to name a few. Scientists across the globe are spending their entire careers evaluating the myriad biological effects of these fatty acids. Although we still do not know precisely how DHA and EPA will fit into our medicinal armamentarium, we do know that they have an important role to play. More studies and clinical trials are needed. One thing is clear however. DHA and EPA are here to stay. They represent a component in our diets that should be emphasized, not neglected. Nearly daily fatty fish or fish oils should be a part of most people’s dietary habits.

Beyond the value of DHA and EPA is an even more important message though. The media, in their unbridled attempt to produce quick and enticing stories, often critically misses the mark. Consequently we all must be very careful about how we interpret what we read or hear. We must always be vigilant when drawing conclusions about our health as well as other consequential matters.

Recently, on a medical sojourn, I was met at the airport by a garrulous woman driver. She was a young-appearing fifty year old who as it turns out had recently sustained a TIA, or “mini-stroke.” Although my first thought was atrial fibrillation, she actually had developed a near occlusion of her left carotid artery. Her right carotid artery, she informed me, had a mere 40% stenosis. Our discussion continued and I gleaned that she had a very strong family history of early onset vascular disease, several close relatives even dying quite young from their events. So my next thought was Familial Hypercholesterolemia. But no, her LDL was apparently normal. Then she fessed up. She had been – and continued to be – a smoker. Just like everyone else in her family! Shocking.

To smoke cigarettes nowadays is something I simply cannot wrap my head around. Cancer, stroke, heart disease, lung disease, wrinkles… Tobacco is devoid of any redeeming quality. It’s just plain bad. So why would anyone smoke in the first place? But, once an individual has experienced a near death event that is a direct consequence of tobacco, how in the world could she continue to smoke. My 40-minute drive took on a mission. I was going to get her to quit. I asked about her children and even grandchildren. We spoke about loss of limbs, dependence upon an oxygen tank, facial cancers and their attendant disfigurement, another stroke – the next one of course placing her in a wheel chair, unable to speak or care for herself. Then she dropped me at my destination. She was to pick me up several hours later. Before stepping out of the car I told her with stern authority that a cigarette should never again cross her lips. Chew gum I said. Gain weight if you must, but please don’t ever come near another cigarette. (I must confess; my tone was intentionally severe and perhaps even paternal. The impact I hoped would justify my behavior.)

I went through my day, completed my tasks, and eagerly awaited her return. Upon her arrival she stepped from the car and proudly and loudly through a mouthful of gum intoned that she had done it. She quit smoking. I am not certain whether her resolution will last an hour or a lifetime. For that moment though she was no longer a smoker. A gum chewer yes, but not a smoker.

Incessantly the media, scientists, doctors, self-proclaimed experts of this or that pronounce they have found the answer to some burning issue. Mostly the matters involve health. What fat is best, or are carbohydrates better than saturated fats, or is fish oil really any good, or is the rampant use of statins the product of evil pharmaceutical propaganda. The list is interminable. And everyone has a voice. Actors and actresses somehow as a consequence of their on-screen fame have absorbed knowledge beyond that which is possessed by even our greatest scientists. Newscasters weigh in and authors sell their latest tomes with promises of truth. The whole dance of the experts would be quite amusing were it not so dangerous.

What seems to be missing from all those who have managed to communicate so easily with the almighty is a sense of responsibility. When people voice their opinions with such certitude, and their audience believes in their veracity with such solidarity, what is truly opinion then masquerades as fact. As a consequence, fiery battles flare among opposing sides. The vegans pound their fists shouting, “Not even a drop of oil! No fat at all!” The Wheat Belly folk eschew the grains, while the dairy exorcists discard the milk, and the Atkins aficionados chow down on meat and more meat. Get them together on TV and you have a firestorm.

Now bring in the politicians and celebrities. They take whatever “science” they find most convincing and try to turn it into law. No large sodas for the sugar busters; no trans fats for practically everyone (that one I have to admit is compelling), nothing with a face for the vegans. In short order there won’t be much left to eat at all.

I have my own take on the diet issue. In short I’m fairly certain we are all quite different, and consequently do better with different diets. As a generalization though I’d recommend moderation in all things, avoiding processed foods, eating a balanced diet, maintaining an optimal weight, and exercising daily. Perhaps that prescription would make a good law.

Fundamentally it comes down to this. We should all be permitted to eat whatever we wish as long as it doesn’t harm anyone but us. Government should not have the right to tell an individual what he or she can or cannot consume. There is a key caveat though. This holds true, “as long as it doesn’t hurt anyone else.” So what do we do about the ailments that occur as a consequence of food-induced obesity – diabetes for one? Do we penalize the consumers of sugar who as a consequence of their dietary predilections become obese and diabetic? Do they pay higher health insurance premiums? Probably not a popular notion. How about the smokers, should everyone foot the bill for his or her heart disease, COPD, and lung cancer treatments? Clearly these issues are slippery slopes, ones upon which I have no desire to tread.

I will emphasize one point however, and of this I am sure. No one knows what diet is best for all mankind. And until such a discovery is made, creating a food police force is probably not a good idea at all.